Antibiotics | Piper nigrum Extract as an Adjuvant in a Collagen System for Infected Wound Healing: Therapeutic Synergy and Biocompatibility

This study developed a collagen-based composite supplemented with Piper nigrum extract for localized treatment of infected wounds. Piper nigrum extract exhibits strong antioxidant, antibacterial, and biocompatible properties, and synergizes with Cefazolin to enhance antibiotic effectiveness. This composite shows promising potential for managing chronic infected wounds.

 

Literature Overview
The article 'Piper nigrum Extract as an Adjuvant in a Collagen System for Infected Wound Healing: Therapeutic Synergy and Biocompatibility' published in the journal Antibiotics reviews and summarizes the challenges in healing chronic infected wounds and the natural bioactive properties of Piper nigrum extract. The study highlights the potential of plant extracts in promoting wound repair, particularly through antioxidant, anti-inflammatory, and antibacterial functions, offering new strategies for treating chronic wounds.

Background Knowledge
Chronic wounds (such as diabetic foot ulcers and venous leg ulcers) experience significantly delayed healing due to oxidative stress, inadequate vascular supply, persistent inflammation, and bacterial infection, posing major challenges for clinical treatment. Conventional antibiotics (e.g., Cefazolin) are effective in treating infections but have limited efficacy against Gram-negative bacteria and long-term use may lead to increased drug resistance. Piper nigrum L. extract is rich in polyphenols and alkaloids (such as piperine), offering broad antioxidant, antibacterial, and anti-inflammatory effects. Previous studies have shown that Piper nigrum extract can reduce microbial burden, enhance collagen deposition, and promote wound healing by modulating the EGFR pathway. This study aims to incorporate Piper nigrum extract into a collagen-arginine composite system to enhance antibiotic activity and promote wound repair. Additionally, the study combines structural bioinformatics approaches, using platforms like SwissADME and DeepPK to predict pharmacokinetics and pharmacodynamics of compounds in Piper nigrum extract, providing theoretical support for future development.

 

 

Research Methods and Experiments
The research team extracted polyphenols from Piper nigrum seeds using ultrasound-assisted extraction, and conducted chemical composition analysis of the extract using UHPLC-MS/MS and colorimetric methods. Antioxidant capacity was evaluated using DPPH, CUPRAC, FRAP, and TEAC assays, while antimicrobial activity was analyzed using MIC, MBC, and MBEC tests. Synergistic effects between Piper nigrum extract and Cefazolin were evaluated across various bacterial strains. Furthermore, structural and stability characteristics of the collagen-arginine-Piper nigrum extract composite powder were analyzed using FTIR, SEM, TGA-DSC, and DLS techniques. Cell-based experiments assessed the biocompatibility of the material, its protective effects on keratinocytes, and its activity in an AAPH-induced oxidative stress model.

Key Conclusions and Perspectives

• The Piper nigrum extract is rich in polyphenolic compounds, including phenolic acids, stilbenes, anthocyanins, and flavonoids, which demonstrate significant antioxidant capacity through electron transfer mechanisms (FRAP, CUPRAC) to neutralize free radicals.
• FTIR and SEM analyses confirmed the successful integration of Piper nigrum extract into the collagen-arginine matrix without causing protein denaturation, and TGA-DSC data indicated good thermal stability of the material at moderate concentrations.
• The extract exhibits antimicrobial and antibiofilm activity against various bacterial species, including both Gram-positive and Gram-negative bacteria, and demonstrates synergistic or additive effects with Cefazolin at moderate doses, significantly enhancing antibiotic efficacy.
• In vitro cell experiments showed that the composite material has excellent biocompatibility, is non-toxic to keratinocytes, and effectively protects cells from oxidative stress damage induced by AAPH.
• Structural bioinformatics analysis revealed that certain compounds in Piper nigrum extract can bind to specific targets (e.g., MAO-B, CDK2, FABP4), potentially influencing neuroprotection, cell cycle regulation, and lipid metabolism.

Research Significance and Prospects
This study presents a multifunctional composite material for localized treatment of chronic infected wounds by combining natural antioxidant and antibacterial components with a modern drug delivery system. Future research should further evaluate the in vivo efficacy of this material in animal models and explore its potential for clinical application. Additionally, the molecular mechanisms of specific compounds within the extract require deeper investigation to clarify their exact roles in wound healing.

 

 

Conclusion
This study successfully developed a collagen-arginine composite powder based on Piper nigrum extract and evaluated its performance in antibacterial, antioxidant, and biocompatibility aspects. Piper nigrum extract shows good thermal stability at moderate concentrations, synergizes with Cefazolin for enhanced antibacterial effects, and demonstrates protective effects in cell models. These findings suggest that the composite holds promise for chronic wound treatment. Bioinformatics analysis also revealed potential molecular targets of certain compounds in the extract, providing theoretical support for future drug development. By combining the bioactivity of natural products with the structural advantages of collagen matrices, this material offers opportunities for further optimization of drug delivery performance and evaluation in animal models and clinical settings.

 

Virgina Silviana Becherescu Barbu, Ioana Cristina Marinas, Diana Madalina Gaboreanu, Alice-Stefania Serbanoiu, and Speranta Avram. Piper nigrum Extract as an Adjuvant in a Collagen System for Infected Wound Healing: Therapeutic Synergy and Biocompatibility. Antibiotics.